CDCA7

protein-coding

cell division cycle associated 7

Gene summary

This gene was identified as a c-Myc responsive gene, and behaves as a direct c-Myc target gene. Overexpression of this gene is found to enhance the transformation of lymphoblastoid cells, and it complements a transformation-defective Myc Box II mutant, suggesting its involvement in c-Myc-mediated cell transformation. Two alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

MANE transcript

NM_031942.5

Inheritance

ClinVar variants

P:4U:124B:84

Top phenotype

Immunodeficiency-centromeric instability-facial anomalies syndrome 3

gnomAD constraint

pLI —, LoF o/e 0.32

Max pathogenic AF

—

Genomic locus

chr2:173,354,820-173,368,997

External References & Databases

Ensembl (ENSG00000144354)

Transcript & Mutation Effects

hg38 • Region Span ~14.2 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

immunodeficiency-centromeric instability-facial anomalies syndrome 3STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0014828

Submitter: Labcorp Genetics (formerly Invitae)

immunodeficiency-centromeric instability-facial anomalies syndromeSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0000133

Submitter: Orphanet

immunodeficiency-centromeric instability-facial anomalies syndrome 3MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0014828

Submitter: ClinGen

CDCA7 was first reported in relation to autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome 3 in 2015 (Thijssen et al., PMID: 26216346). This condition is characterized by recurrent infection, dysmorphic facial features, developmental delay and hypomethylation of certain chromosomal regions. The phenotypic presentation varied among patients reported. Five variants (missense and nonsense) that have been reported in six probands in three publications (PMIDs: 26216346, 33726816, 39320531) are included in this curation. Variants segregated with disease in one family. Heterozygous parents were unaffected. The mechanism of pathogenicity is suspected to be loss of function. All reported missense mutations are located in the conserved C-terminal zinc finger domain. This gene-disease association is also supported by protein interactions, biochemical function, functional alteration in patient and non-patient cells, and non-human model organism (PMID: 29339483, 30307408, 26216346, 25385755, 41370347). In summary, there is moderate evidence to support this gene-disease relationship. While more evidence is needed to establish this relationship definitively, no convincing contradictory evidence has emerged. This gene-disease pair was originally evaluated by the SCID/CID GCEP on May 02, 2023. It was re-evaluated on April 16, 2026. As a result of this reevaluation, the classification increased from Limited to Moderate with the addition of a new case and experimental study (PMIDs: 39320531, 41370347).

Clinical Genomic Database (CGD)

Immunodeficiency-centromeric instability-facial anomalies syndrome 3AR

Manifestation: Allergy/Immunology/Infectious; Craniofacial; Gastrointestinal; Neurologic

Intervention: Allergy/Immunology/Infectious

Rationale: Individuals have been described with recurrent childhood infections, and awareness may allow prompt and aggressive treatment of infections

Refs: 15952214; 1999836; 26216346

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CDCA7 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 257

not specifiedTotal: 69

Immunodeficiency-centromeric instability-facial anomalies syndrome 3Total: 15

CDCA7-related disorderTotal: 7

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031942.5. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	76 clinvar	3 clinvar	83
missense		4 clinvar	103 clinvar	5 clinvar		112
nonsense			4 clinvar			4
start loss						0
frameshift			7 clinvar			7
splice donor/acceptor (+/-2bp)			6 clinvar			6
Total	0	4	124	81	3	212

Highest pathogenic variant AF is 0.000010532485

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 52 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031942.5	RefSeq	NP_114148.3	10	MANE Select
ENST00000306721.8	Ensembl	ENSP00000306968.3	10	MANE Select
NM_145810.3	RefSeq	NP_665809.1	9	Standard
ENST00000347703.7	Ensembl	ENSP00000272789.4	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
cdca7a	Danio rerio	Structure: whole organism Quality: has fewer parts of type abnormal

Gene / Model

Organism

Observed Phenotype

cdca7a

Danio rerio

Structure: whole organism

Quality: has fewer parts of type

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Validated targets of C-MYC transcriptional activation

Biological Process

regulation of transcription, DNA-templated
apoptotic process
regulation of cell population proliferation

Cellular Component

nucleus
nucleoplasm
cytosol

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000306721
Coding exons: 10
Length: 14178
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 24
Defined: 125748
p: 0.0000954

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.59	203	277	0.732	0.0000172	2959
Missense (PolyPhen)		69	106.7	0.64665		1222
Synonymous	1.73	80	102	0.782	0.00000640	847
Loss of Function	3.12	8	24.8	0.323	0.00000147	287

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00014	0.00014	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000089	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Participates in MYC-mediated cell transformation and apoptosis; induces anchorage-independent growth and clonogenicity in lymphoblastoid cells. Insufficient to induce tumorigenicity when overexpressed but contributes to MYC-mediated tumorigenesis. May play a role as transcriptional regulator. {ECO:0000269|PubMed:11598121, ECO:0000269|PubMed:15994934, ECO:0000269|PubMed:16580749, ECO:0000269|PubMed:23166294}.;
Disease: DISEASE: Immunodeficiency-centromeric instability-facial anomalies syndrome 3 (ICF3) [MIM:616910]: A rare disorder characterized by a variable immunodeficiency resulting in recurrent infections, facial anomalies, and branching of chromosomes 1, 9, and 16. Other variable symptoms include growth retardation, failure to thrive, and psychomotor retardation. Laboratory studies show limited hypomethylation of DNA in a small fraction of the genome in some, but not all, patients. {ECO:0000269|PubMed:26216346}. Note=The disease may be caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.734
RVIS EVS: -0.69
RVIS percentile EVS: 14.97

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.419

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium